Assessing risk of bias:a proposal for a unified framework for observational studies and randomized trials

BACKGROUND: Evidence based medicine aims to integrate scientific evidence, clinical experience, and patient values and preferences. Individual health care professionals need to appraise the evidence from randomized trials and observational studies when guidelines are not yet available. To date, tools for assessment of bias and terminologies for bias are specific for each study design. Moreover, most tools appeal only to methodological knowledge to detect bias, not to subject matter knowledge, i.e. in-depth medical knowledge about a topic. We propose a unified framework that enables the coherent assessment of bias across designs. METHODS: Epidemiologists traditionally distinguish between three types of bias in observational studies: confounding, information bias, and selection bias. These biases result from a common cause, systematic error in the measurement or common effect of the intervention and outcome respectively. We applied this conceptual framework to randomized trials and show how it can be used to identify bias. The three sources of bias were illustrated with graphs that visually represent researchers' assumptions about the relationships between the investigated variables (causal diagrams). RESULTS: Critical appraisal of evidence started with the definition of the research question in terms of the population of interest, the compared interventions and the main outcome. Next, we used causal diagrams to illustrate how each source of bias can lead to over- or underestimated treatment effects. Then, we discussed how randomization, blinded outcome measurement and intention-to-treat analysis minimize bias in trials. Finally, we identified study aspects that can only be appraised with subject matter knowledge, irrespective of study design. CONCLUSIONS: The unified framework encompassed the three main sources of bias for the effect of an assigned intervention on an outcome. It facilitated the integration of methodological and subject matter knowledge in the assessment of bias. We hope that graphical diagrams will help clarify debate among professionals by reducing misunderstandings based on different terminology for bias

“Catch 22”: biosecurity awareness, interpretation and practice amongst poultry catchers

Campylobacter contamination of chicken on sale in the UK remains at high levels and has a substantial public health impact. This has prompted the application of many interventions in the supply chain, including enhanced biosecurity measures on-farm. Catching and thinning are acknowledged as threats to the maintenance of good biosecurity, yet the people employed to undertake this critical work (i.e. ‘catchers’) are a rarely studied group. This study uses a mixed methods approach to investigate catchers’ (n = 53) understanding of the biosecurity threats posed by the catching and thinning, and the barriers to good biosecurity practice. It interrogated the role of training in both the awareness and practice of good biosecurity. Awareness of lapses in biosecurity was assessed using a Watch-&-Click hazard awareness survey (n = 53). Qualitative interviews (n = 49 catchers, 5 farm managers) explored the understanding, experience and practice of catching and biosecurity. All of the catchers who took part in the Watch-&-Click study identified at least one of the biosecurity threats with 40% detecting all of the hazards. Those who had undergone training were significantly more likely to identify specific biosecurity threats and have a higher awareness score overall (48% compared to 9%, p = 0.03). Crucially, the individual and group interviews revealed the tensions between the high levels of biosecurity awareness evident from the survey and the reality of the routine practice of catching and thinning. Time pressures and a lack of equipment rather than a lack of knowledge appear a more fundamental cause of catcher-related biosecurity lapses. Our results reveal that catchers find themselves in a ‘catch-22′ situation in which mutually conflicting circumstances prevent simultaneous completion of their job and compliance with biosecurity standards

Design characteristics of studies on medical practice variation of caesarean section rates : A scoping review

Peer reviewedPublisher PD

Developing quality indicators for the care of HIV-infected pregnant women in the Dutch Caribbean

<p>Abstract</p> <p>Background</p> <p>Effective interventions to prevent mother-to-child HIV transmission (PMTCT) exist and when properly applied reduce the risk of vertical HIV transmission. As part of optimizing PMTCT in the Dutch Caribbean we developed a set of valid and applicable indicators in order to assess the quality of care in HIV-infected (pregnant) women and their newborns.</p> <p>Methods</p> <p>A multidisciplinary expert panel of 19 experts reviewed and prioritized recommendations extracted from locally used international PMTCT guidelines according to a 3-step-modified-Delphi procedure. Subsequently, the feasibility, sample size, inter-observer reliability, sensitivity to change and case mixed stability of the potential indicators were tested for a data set of 153 HIV-infected women, 108 pregnancies of HIV-infected women and 79 newborns of HIV-infected women in Aruba, Curaçao and St Maarten from 2000 to 2010.</p> <p>Results</p> <p>The panel selected and prioritized 13 potential indicators. Applicability could not be tested for 4 indicators regarding HIV-screening in pregnant women because of lack of data. Four indicators performed satisfactorily for Curaçao ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'intrapartum antiretroviral therapy and infant prophylaxis if antepartum antiretroviral therapy was not received', 'scheduled caesarean delivery') and 3 for St Maarten ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'discuss and provide combined antiretroviral therapy to all HIV-infected pregnant women') whilst none for Aruba.</p> <p>Conclusions</p> <p>A systemic evidence-and consensus-based approach was used to develop quality indicators in 3 Dutch Caribbean settings. The varying results of the applicability testing accentuate the necessity of applicability testing even in, at first, comparable settings.</p

Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification

Secondary piperidines are ideal pharmaceutical building blocks owing to the prevalence of piperidines in commercial drugs. Here, we report an electrochemical method for cyanation of the heterocycle adjacent to nitrogen without requiring protection or substitution of the N–H bond. The reaction utilizes ABNO (9-azabicyclononane N-oxyl) as a catalytic mediator. Electrochemical oxidation of ABNO generates the corresponding oxoammonium species, which promotes dehydrogenation of the 2° piperidine to the cyclic imine, followed by addition of cyanide. The low-potential, mediated electrolysis process is compatible with a wide range of heterocyclic and oxidatively sensitive substituents on the piperidine ring and enables synthesis of unnatural amino acids

The use of quality information by general practitioners: does it alter choices? A randomized clustered study

Background: Following the introduction of elements of managed competition in the Netherlands in 2006, General Practitioners (GPs) and patients were given the role to select treatment hospital using public quality information. In this study we investigate to what extent hospital preferences of GP's are affected by performance indicators on medical effectiveness and patient experiences. We selected three conditions: breast cancer, cataract surgery, and hip and knee replacement. Methods. After an inquiry 26 out of 226 GPs in the region signed up to participate in our study. After a 2:1 randomization, we analyzed the referral patterns in the region using three groups of GPs: GPs (n=17) who used the report cards and received personal clarification, GPs that signed up for the study but were assigned to the control group (n=9), and the GPs outside the study (n=200).We conducted a difference in differences analysis where the choice for a particular hospital was the dependent variable and time (2009 or 2010), the sum score of the CQI, the sum score of the PI's and dummy variables for the individual hospitals were used as independent variables. Results: The analysis of the conditions together and cataract surgery and hip and knee replacement separately, showed no significant relationships between the scores on the report cards and the referral patterns of the GPs. For breast cancer our analysis revealed that GPs in the intervention group refer 1.0% (p=0.01) more to hospitals that score one percent point better on the indicators for medical effectiveness. Conclusion: Our study provides empirical evidence that GP referral patterns were unaffected by the available quality information, except for the outcome indicators for breast cancer care that were presented. This finding was surprising since our study was designed to identify changes in hospital preference (1) amongst the most motivated GP's, (2) that received personal clarification of the performance indicators, and (3) selected indicators/conditions from a large set of indicators that they believed were most important. This finding may differ when quality information is based on outcome indicators with a clinically relevant difference, as shown by our indicators for breast cancer treatment. We believe that the current set of (largely process) hospital quality indicators do not serve the GP's information needs and consequently quality plays little role in the selection of hospitals for treatment. © 2013 Ikkersheim and Koolman; licensee BioMed Central Ltd

CT pulmonary angiography: an over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism

Aims: To determine if computed tomographic pulmonary angiography (CTPA) was overemployed in the evaluation of hospitalized patients with suspected acute pulmonary embolism (PE). Methods: Data were gathered retrospectively on hospitalized patients (n=185) who had CTPA for suspected PE between June and August 2009 at our institution. Results: CTPA was done in 185 hospitalized patients to diagnose acute PE based on clinical suspicion. Of these, 30 (16.2%) patients were tested positive for acute PE on CTPA. The Well&#x0027;s pretest probability for PE was low, moderate, and high in 77 (41.6%), 83 (44.9%), and 25 (13.5%) patients, respectively. Out of the 30 PE-positive patients, pretest probability was low in 2 (6.6%), moderate in 20 (66.7%), and high in 8 (26.6%) (p=0.003). Modified Well&#x0027;s criteria applied to all patients in our study revealed 113 (61%) with low and 72 (39%) with high clinical pretest probability. When modified Well&#x0027;s criteria was applied to 30 PE-positive patients, 10 (33.3%) and 20 (66.6%) were found to have low and high pretest probability, respectively (p=0.006). D-dimer assay was done in 30 (16.2%) of the inpatients with suspected PE and all of them were found to have elevated levels. A lower extremity duplex ultrasound confirmed deep venous thrombosis in 17 (9.1%) of the patients with suspected PE, at least 1 week prior to having CTPA. Conclusion: Understanding the recommended guidelines, evidence-based literature, and current concepts in evaluation of patients with suspected acute PE will reduce unnecessary CTPA examinations

Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

Background: Research is fundamental to high-quality care, but concerns have been raised about whether health research is conducted in the populations most affected by high disease prevalence. Geographical distribution of research activity is important for many reasons. Recruitment is a major barrier to research delivery, and undertaking recruitment in areas of high prevalence could be more efficient. Regional variability exists in risk factors and outcomes, so research done in healthier populations may not generalise. Much applied health research evaluates interventions, and their impact may vary by context (including geography). Finally, fairness dictates that publically funded research should be accessible to all, so that benefits of participating can be fairly distributed. We explored whether recruitment of patients to health research is aligned with disease prevalence in England. Methods: We measured disease prevalence using the Quality and Outcomes Framework in England (total long-term conditions, mental health and diabetes). We measured research activity using data from the NIHR Clinical Research Network. We presented descriptive data on geographical variation in recruitment rates. We explored associations between the recruitment rate and disease prevalence rate. We calculated the share of patient recruitment that would need to be redistributed to align recruitment with prevalence. We assessed whether associations between recruitment rate and disease prevalence varied between conditions, and over time. Results: There was significant geographical variation in recruitment rates. When areas were ranked by disease prevalence, recruitment was not aligned with prevalence, with disproportionately low recruitment in areas with higher prevalence of total long-term and mental health conditions. At the level of 15 local networks, analyses suggested that around 12% of current recruitment activity would need to be redistributed to align with disease prevalence. Overall, alignment showed little change over time, but there was variation in the trends over time in individual conditions. Conclusions: Geographical variations in recruitment do not reflect the suitability of the population for research. Indicators should be developed to assess the fit between research and need, and to allow assessment of interventions among funders, researchers and patients to encourage closer alignment between research activity and burden

Terrisporobacter hibernicus sp. nov., isolated from bovine faeces in Northern Ireland

A new species of Terrisporobacter, a Gram-positive, spore-forming anaerobic group, proposed name Terrisporobacter hiberni-cus sp. nov., was isolated in Northern Ireland from bovine faeces collected in 2016. Designated as MCA3T, cells of T. hibernicus sp. nov. are rod shaped and motile. Cells tolerate NaCl from 0.5 to 5.5 % (w/v), with a pH tolerance between pH 6 and 9. The optimal temperature for growth is 35–40 °C, and temperatures from 20 to 30 °C are tolerated. The polar lipid profile displays diphosphatidylglycerol, phosphatidylglycerol, two aminoglycolipids, one glycophospholipid, one aminolipid, three glycolipids, five phospholipids and one lipid. No respiratory quinones are detected. The predominant fatty acid profile includes C16: 0 at 22.8 %. Strain MCA3T is positive for glucose and maltose acidification, as well as glycerol and sorbitol. The biochemical results from a VITEK2 assay of strain MCA3T, Terrisporobacter petrolearius LAM0A37T and Terrisporobacter mayombei DSM 6539T are also included for the first time. The closed and complete genome of strain MCA3T from a hybrid Oxford Nanopore Technology MinION/Illumina assembly reveals no evidence for known virulence genes. Draft genome sequencing of T. mayombei DSM 6539T and T. petrolearius LAM0A37T, as performed by Illumina MiSeq, provides reference genomes for these respective species of Terrisporobacter for the first time. DNA–DNA hybridization values (d4) of MCA3T to Terrisporobacter glycolicus ATCC 14880T, T. petrolearius LAM0A37T and T. mayombei DSM 6539T are 48.8, 67.4 and 46.3 %, with cutoff value at 70 %. The type strain for T. hibernicus sp. nov. is MCA3T (=NCTC 14625T=LMG 32430T)

Measuring and explaining mortality in Dutch hospitals; The Hospital Standardized Mortality Rate between 2003 and 2005

Background. Indicators of hospital quality, such as hospital standardized mortality ratios (HSMR), have been used increasingly to assess and improve hospital quality. Our aim has been to describe and explain variation in new HSMRs for the Netherlands. Methods. HSMRs were estimated using data from the complete population of discharged patients during 2003 to 2005. We used binary logistic regression to indirectly standardize for differences in case-mix. Out of a total of 101 hospitals 89 hospitals remained in our explanatory analysis. In this analysis we explored the association between HSMRs and determinants that can and cannot be influenced by hospitals. For this analysis we used a two-level hierarchical linear regression model to explain variation in yearly HSMRs. Results. The average HSMR decreased yearly with more than eight